Evaluation of drugs for potential repurposing against COVID-19 using a tier-based scoring system

Abstract

<jats:sec><jats:title>Background</jats:title><jats:p> As the coronavirus disease 2019 (COVID-19) pandemic grows daily, we remain with no prophylactic and only minimal therapeutic interventions to prevent or ameliorate severe acute respiratory syndrome Corona-virus 2 (SARS-CoV-2). Prior to SARS-CoV-2 emergence, high throughput screens utilizing clinically developed drugs identified compounds with in vitro inhibitory effect on human coronaviruses that may have potential for repurposing as treatment options for COVID-19. However, caution should be applied to repurposing of these drugs when they are taken out of context of human pharmacokinetic parameters associated with normal therapeutic use. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Our aim was to provide a tier-based scoring system to interrogate this data set and match each drug with its human pharmacokinetic criteria, such as route of administration, therapeutic plasma levels and half-life, tissue distribution and safety. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Our analysis excluded most previously identified drugs but identified members of four drug classes (anti-malarial amino-quinolones, selective estrogen receptor modulators [SERMs], low potency tricyclic antipsychotics and tricyclic antidepressants) as potential drug candidates for COVID-19. Two of them, the tricyclic antipsychotics and tricyclic antidepressants were further excluded based on a high adverse event profile. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> In summary, our findings using a new pharmacokinetic-based scoring system supports efficacy testing of only a minority of candidates against SARS-CoV-2 infection. </jats:p></jats:sec>